Project Summary/Abstract Electronic cigarettes (ECIGs) are a novel class of tobacco products that vaporize a liquid, often containing nicotine, into an aerosol that users inhale. ECIG popularity is increasing in the US and the growing number of ECIG users reporting frequent, daily use suggests that these products may have tobacco cigarette-like abuse liability. ECIG abuse liability could be influenced by factors that impact nicotine delivery, such as device power, liquid nicotine concentration, and user puffing behavior such as puff number and duration (i.e., puff topography). Another factor that likely influences ECIG abuse liability is flavor, and there are over 7,000 unique ECIG liquid flavors available on the US market many of which are sweet flavors. Not surprisingly, many of these liquids use added sweeteners such as sucralose. Perceived sweetness increases ECIG appeal and thus may enhance ECIG abuse liability. The current study has two aims. Aim 1 will use multiple clinical abuse liability assessments to determine how a common ECIG liquid sweetener, sucralose, influences ECIG abuse liability in cigarette smokers using a within subjects, Latin-square order design. Participants will come to the clinical behavioral psychopharmacology research laboratory to complete five sessions that include an own brand cigarette positive control and four ECIG conditions all using a 30 Watt ECIG filled with liquid that is either 0 or 6 mg/ml nicotine and is either unsweetened or sweetened with sucralose. Abuse liability will be measure via a progressive-ratio task (PRT), modified CPT, blood nicotine delivery, and multiple subjective state measures. Aim 2 will investigate how sweeteners influence toxicant yield using puffing behaviors recorded in Aim 1. Using playback technology, puff topography for participants in Aim 1 will be used to generate aerosols that will be analyzed for aldehydes, furans, and chloropropanols. The primary hypotheses are that 1) PRT breakpoint will increase with liquid nicotine and with sweetener, such that participants will perform more work for puffs when using the 6 mg/ml, sweetened liquid, though the greatest breakpoint will be observed for puffs from own brand cigarettes and 2) that sucralose will increase aerosol toxicants as a result of thermal degradation and longer and larger puffs. Results will address factors influencing ECIG user dependence and health risks and may inform ECIG regulation. Furthermore, the current proposal contains a comprehensive training plan that will advance the applicant's expertise in the areas of clinical behavioral pharmacology, clinical epidemiology, drug policy, and psychopharmacology, and will also provide the applicant with the opportunity to learn new techniques and methodologies in behavioral economics, chemical toxicology, and epidemiology that will be invaluable as they pursue a career as an independent, poly-drug abuse researcher.